1. Field of the Invention
This invention relates generally to the field of implants for human and animal bodies. In particular, this invention relates to apparatus and methods for controlling tissue/implant interactions, thereby allowing better integration, function, and extended lifespan of implants in the body.
2. Description of the Related Art
Implantable artificial materials and devices, such as drug delivery systems, pacemakers, artificial joints, and organs play an important role in health care today. In addition to these devices, implantable monitoring devices or xe2x80x9cbiosensorsxe2x80x9d have great potential for improving both the quality of care and quality of life of patients and animals. An exemplary monitoring device that would greatly improve the quality of life for diabetic patients and animals, for example, is an implantable glucose monitor for the pain-free, continuous, reliable monitoring of blood glucose levels. Diabetic patients presently monitor their own glucose blood levels by obtaining samples of capillary blood through repeated finger-pricking. Because the tests are painful, time-consuming, and must be performed multiple times throughout a single day, diabetic patients resist performing an adequate number of daily tests. This low compliance exacerbates the intrinsically discontinuous nature of the monitoring, and ultimately leads to the extensive pathology associated with diabetic patients.
One of the major problems associated with all types of implants is biocompatibility of the implant with the body, and in particular with the tissue adjacent to the site of the implant. For example, despite attempts to design implantable biosensors for glucose and other monitoring functions, none developed to date provide pain-free, reliable and continuous monitoring. One reason is that current implantable sensors suffer from a progressive loss of function after relatively short periods of time in vivo. This loss in function arises from multiple factors, some of the most important of which include protein adsorption, inflammation, and fibrosis (encapsulation) resulting from tissue trauma at the site of the implant. This fibrosis results in loss of blood vessels at the site of implantation and therefore in a reduced access to blood glucose levels. These factors can also interfere with the function of other implants and implantable devices, such as insulin pumps, pacemakers, artificial joints, and artificial organs.
One approach to control the inflammation and fibrosis resulting from tissue trauma at the site of implantation has been to use inert materials such as titanium or single-crystalline alumina, as disclosed in U.S. Pat. No. 4,122,605 to Hirabayashi et al. While suitable for bone or tooth implants, this approach is not useful in more complex prosthetic devices or in biosensors, which requires use of a variety of materials. Another approach has been the use of a porous, outer coating of DACRON or TEFLON, as disclosed in U.S. Pat. No. 4,648,880 to Brauman et al., or with polytetrafluorethylene, as disclosed in U.S. Pat. No. 5,779,734. While suitable for prostheses such as breast implants, such coatings are not practical for prosthetic devices or biosensors having complex geometries. The most commonly-used approach to control tissues responses, particularly inflamation, has been the systemic administration of drugs such as corticosteroids. Such systemic administration can result in side effects such as generalized immunosupression, bloating, and psychiatric problems, especially over the long term. There accordingly remains a need in the art for apparatus and methods for controlling tissue/implant interactions, particularly for implantable materials, prostheses, and devices such as biosensors.
The above-discussed and other drawbacks and deficiencies of the prior art are overcome or alleviated by an improved tissue/implant interface, comprising an implant having an outer surface and a bioactive polymer layer adjacent to at least a portion of the outer surface of the implant. In a preferred embodiment, the polymer layer contains at least one tissue response modifier covalently attached to the polymer layer or entrapped within the polymer layer in a quantity effective to control the tissue response at the site of implantation. The bioactive polymer layer may be a synthetic organic polymer such as a hydrogel, or a natural polymer such as a protein. The polymer may also be self-assembled. Preferably, the at least one tissue response modifier controls inflammation, fibrosis, cell migration, cell proliferation, leukocyte activation, leukocyte adherence, lymphocyte activation, lymphocyte adherence, macrophage activation, macrophage adherence, cell death and/or neovascularization. Exemplary tissue response modifiers include, but are not limited to, steroidal and non-steroidal anti-inflammatory agents, anti-fibrotic agents, anti-proliferative agents, cytokines, cytokine inhibitors, neutralizing antibodies, adhesive ligands, metabolites and metabolic intermediates, DNA, RNA, cytotoxic agents, and combinations thereof. The tissue response modifiers may be covalently attached to the polymer layer or entrapped within the polymer layer.
In another embodiment, the tissue response modifier is covalently attached to the polymer layer or entrapped within the polymer layer in slow-release form, for example in the form of biodegradable polymers, nanoparticles, liposomes, emulsions, and microspheres, to provide long-term delivery of the tissue response modifier to the site of implantation.
The addition of the various combinations of tissue response modifiers with bioactive polymers provides an extremely simple, flexible and effective means to control the implant/tissue interphase, improving implant lifetime and function. The above-discussed and other features and advantages will be appreciated and understood by those skilled in the art from the following detailed description and drawings.